Responses of Clostridia to oxygen: from detoxification to adaptive strategies

Abstract

Clostridia comprise bacteria of environmental, biotechnological and medical interest and many commensals of the gut microbiota. Because of their strictly anaerobic lifestyle, oxygen is a major stress for Clostridia. However, recent data showed that these bacteria can cope with O 2 better than expected for obligate anaerobes through their ability to scavenge, detoxify and consume O 2 . Upon O 2 exposure, Clostridia redirect their central metabolism onto pathways less O 2 -sensitive and induce the expression of genes encoding enzymes involved in O 2 -reduction and in the repair of oxidized damaged molecules. While Faecalibacterium prausnitzii efficiently consumes O 2 through a specific extracellular electron shuttling system requiring riboflavin, enzymes such as rubrerythrins and flavodiiron proteins with NAD(P) H-dependent O 2 -and/or H 2 O 2 -reductase activities are usually encoded in other Clostridia. These two classes of enzymes play indeed a pivotal role in O 2 tolerance in Clostridioides difficile and Clostridium acetobutylicum. Two main signalling pathways triggering O 2 -induced responses have been described so far in Clostridia. PerR acts as a key regulator of the O 2 -and/or reactive oxygen species-defence machinery while in C. difficile, σ B , the sigma factor of the general stress response also plays a crucial role in O 2 tolerance by controlling the expression of genes involved in O 2 scavenging and repair systems.

Clostridioides difficile strain-dependent and strain-independent adaptations to a microaerobic environment

“…A common example in obligate aerobes is the conversion of superoxide radicals to hydrogen peroxide by superoxide dismutase (SOD) followed by conversion of hydrogen peroxide to water and molecular oxygen by catalase. Rubrerythrin peroxidases and superoxide reductases similarly detoxify ROS in many anaerobic bacteria [32]. While C.…”

“…Previous studies largely focused on the short-term C. difficile oxidative shock response [ 16, 17 ]. However, many bacteria considered to be strict anaerobes, such as Clostridia , can tolerate and grow in oxic environments [ 32 ]. We hypothesized that exposure to low oxygen over time initiates a transcriptional response that is distinct from rapid exposure to high concentrations of oxygen.…”

“…A common example in obligate aerobes is the conversion of superoxide radicals to hydrogen peroxide by superoxide dismutase (SOD) followed by conversion of hydrogen peroxide to water and molecular oxygen by catalase. Rubrerythrin peroxidases and superoxide reductases similarly detoxify ROS in many anaerobic bacteria [ 32 ]. While C. difficile is traditionally cultured under strictly anaerobic conditions, RNA-seq of C. difficile grown with 1.5% oxygen revealed upregulation of several genes that produce factors involved in ROS detoxification.…”

Heterologous Expression of NoxA Confers Aerotolerance in Clostridium sporogenes

“…In addition, there may be intrinsic mechanisms for oxygen tolerance at play, aiding the native culture in these conditions, as has been confirmed for C. botulinum (Camerini et al ., 2019). Studies have shown that Clostridia can cope with oxygen better than might be expected for obligate anaerobes (Lu and Imlay, 2021; Morvan et al ., 2021). However, C. sporogenes has been observed to be more sensitive to oxygen than other Clostridia species (Kawasaki et al ., 1998).…”

Thriving in Oxygen While Preventing ROS Overproduction: No Two Systems Are Created Equal

“…Some of these are intertidal invertebrates, hypoxia-tolerant fish, and desiccation/freeze-tolerant creatures ( Sokolova, 2018 ). A particular case occurs in Clostridium acetobutylicum , a strict anaerobe organism that contains Fe- and Mn-SODs, heme- and Mn-catalases and in addition 1Fe or 2Fe-SORs that reduce the superoxide anion to H 2 O 2 ( Riebe et al, 2009 ; Morvan et al, 2021 ).…”